A5072883486- CAR-T cell therapy research
- Sarcoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Mesenchymal stem cell research
- Platelet Disorders and Treatments
- Virus-based gene therapy research
- Melanoma and MAPK Pathways
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Lung Cancer Research Studies
- Cancer Mechanisms and Therapy
- PARP inhibition in cancer therapy
- Colorectal Cancer Treatments and Studies
- Liver physiology and pathology
- PI3K/AKT/mTOR signaling in cancer
- Glycosylation and Glycoproteins Research
- Cancer Diagnosis and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Cells and Metastasis
Candiolo Cancer Institute
2014-2023
Istituti di Ricovero e Cura a Carattere Scientifico
2014-2023
University of Perugia
1997-2021
University of Turin
1998-2015
Ospedale Sant'Anna
2013
Istituto Ortopedico Rizzoli
2013
Fondazione Piemontese per la Ricerca sul Cancro Onlus
2012
A. O. Ordine Mauriziano di Torino
1999-2009
Kettering University
2004
University of Parma
2004
The enormous plasticity of mesenchymal stem cells (MSCs) suggests an improvement a standard protocol isolation and ex vivo expansion for experimental clinical use. We isolated expanded MSCs from bone marrow (BM) pediatric young adult donors, to analyze the growth kinetic, immunophenotype, telomere length, karyotype during expansion. Seventeen BM samples were collected donors 8 donors. two groups showed no morphological differences while their cell was strictly related donor's age. reached...
Osteosarcoma (OS) is the most common primary bone tumour in children and young adults. Despite improved prognosis, metastatic or relapsed OS remains largely incurable no significant improvement has been observed last 20 years. Therefore, search for alternative agents mandatory.We investigated phospho-ERK 1/2, MCL-1, phospho-Ezrin/Radixin/Moesin (P-ERM) as potential therapeutic targets OS. Activation of these pathways was shown by immunohistochemistry about 70% cases all cell lines analyzed....
The multikinase inhibitor sorafenib displays antitumor activity in preclinical models of osteosarcoma. However, sorafenib-treated patients with metastatic-relapsed osteosarcoma, disease stabilization and tumor shrinkage were short-lived drug resistance occurred. We explored the treatment escape mechanisms to overcome their drawbacks.Immunoprecipitation, Western blotting, immunohistochemistry used analyze mTOR pathway [mTOR complex 1 (mTORC1) 2 (mTORC2)]. Cell viability, colony growth, cell...
We investigate the unknown tumor-killing activity of cytokine-induced killer (CIK) cells against autologous metastatic melanoma and elusive subset putative cancer stem (mCSC).We developed a preclinical model using same patient-generated CIK tumor targets to consider unique biology each patient/tumor pairing. In primary cell cultures, we visualized immunophenotypically defined mCSC novel gene transfer strategy that exploited their exclusive ability activate promoter stemness Oct4.The from 10...
Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable due to the inability eradicate chemoresistant cancer stem-like cells (sCSC) that likely responsible for relapses drug resistance. In this study, we investigated preclinical activity of patient-derived cytokine-induced killer (CIK) against autologous STS, including putative sCSCs. Tumor killing was evaluated both in vitro within an immunodeficient mouse model sarcoma. To identify sCSCs, STS were engineered with...
Enhancing the antitumor activity of DNA-damaging drugs is an attractive strategy to improve current treatment options. Trabectedin isoquinoline alkylating agent with a peculiar mechanism action. It binds minor groove DNA inducing single- and double-strand-breaks. These kinds damage lead activation PARP1, first-line enzyme in DNA-damage response pathways. We hypothesized that PARP1 targeting could perpetuate trabectedin-induced tumor cells leading finally cell death.We investigated...
Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD in allogeneic bone marrow HCT. Here we explore peripheral blood stem transplantation (alloPBSCT). Patients with high-risk received alloPBSCT HLA-matched unrelated/related donors....
Purpose: The MHC-unrestricted activity of cytokine-induced killer (CIK) cells against chemo-surviving melanoma cancer stem (mCSC) was explored, as CSCs are considered responsible for chemoresistance and relapses.Experimental Design: Putative mCSCs were visualized by engineering patient-derived (MC) with a lentiviral vector encoding eGFP under expression control stemness gene promoter oct4 Their potential confirmed in vivo limiting dilution assays. We explored the sensitivity eGFP+ to...
Purpose of our study was to explore a new immunotherapy for high grade soft tissue sarcomas (STS) based on cytokine-induced killer cells (CIK) redirected with chimeric antigen receptor (CAR) against the tumor-promoting CD44v6. We aimed at generating bipotential killers, combining CAR specificity intrinsic tumor-killing ability CIK (CAR+.CIK). set patient-derived experimental platform. CAR+.CIK were generated by transduction precursors lentiviral vector encoding anti-CD44v6-CAR. characterized...
Interferon-induced expression of programmed cell death ligands (PD-L1/PD-L2) may sustain tumour immune-evasion. Patients featuring MET amplification, a genetic lesion driving transformation, benefit from anti-MET treatment. We explored if MET-targeted therapy interferes with Interferon-γ modulation PD-L1/PD-L2 in MET-amplified tumours. and signalling pathways downstream or were analysed lines patient-derived organoids, basal condition, upon stimulation, after therapy. PD-L1 PD-L2 upregulated...
Abstract Purpose: BRAF and MEK inhibitors (BRAF/MEKi) favor melanoma-infiltrating lymphocytes, providing the rationale for current combinatorial trials with anti–PD-1 antibody. A portion of melanoma cells may express PD-1, antibody could have a direct antitumor effect. Here, we explore whether BRAF/MEKi modulate rates PD-1+ cells, supporting an additional—lymphocyte-independent—basis their therapeutic combination Experimental Design: With data mining flow cytometry, assessed PD-L1/2...
No effective therapy is available for unresectable soft-tissue sarcomas (STS). This unmet clinical need prompted us to test whether chondroitin sulfate proteoglycan 4 (CSPG4)-specific chimeric antigen receptor (CAR)-redirected cytokine-induced killer lymphocytes (CAR.CIK) are in eliminating tumor cells derived from multiple STS histotypes vitro and immunodeficient mice.The experimental platform included patient-derived CAR.CIK cell lines established histotypes. were transduced with a...
Malignant Pleural Mesothelioma (MPM) is an aggressive tumor arising from mesothelial cells lining the pleural cavities characterized by resistance to standard therapies. Most of molecular steps responsible for transformation remain unclear; however, several growth factor signaling cascades are known be altered during MPM onset and progression. Transducers these pathways, such as PIK3CA-mTOR-AKT, MAPK, ezrin/radixin/moesin (ERM) could therefore exploited possible targets pharmacological...